Mimicking skin conditions in-vitro (e.g. wounding, aging)

Since human skin models are easy to modulate, different skin conditions such as scar formation, skin aging and wound healing can be mimicked and studied. For this purpose, cells originating from skin tissues representing a certain physiological condition or disease can be isolated, cultured and incorporated into the human skin model. For example, by isolating cells from skin tissue obtained from young and aged individuals we can mimic several processes that occur during skin aging (e.g. thinning of the epidermis, decrease in collagen deposition). Most of these processes are extensively studied in mouse models or in conventional mono cell layers.

By using human skin models we can mimic a micro-environment that is highly similar to that of the in-vivo human tissue, in contrast to conventional monolayer cultures and mouse models. Cells from aged individuals often are characterized by improper protein expression such as collagenase up-regulation and down-regulation of collagen production. Cells that are "aged" in vitro display similar characteristics (e.g. low collagen I deposition, cell senescence, apoptosis, delayed wound healing). In addition, by exposing the skin models to UV, we can also study processes involved in photo aging by looking for example at DNA-damage. Because skin models are easy to handle, different wounds can be introduced. By eliminating a small fragment of the epidermis, a superficial wound is created. It’s also possible to introduce full thickness wounds in order to mimic burn wounds. This approach allows us to investigate processes that occur in for example burn patients. Burn patients are a prime target for infections with their open wounds and long hospital stays. It has recently been reported that multisystem organ failure (for which an infection was responsible in 45.9% of the cases) is the most frequent cause of death of burn patients.

Furthermore, a surgical skin graft is the usual way to restore burned skin, but with bacterial colonization/infections likely such a procedure is often delayed. Moreover, the infectious agents may not respond optimally to the antibiotic treatment as antibiotic resistant strains are often encountered and/or bacteria may form biofilms. In a collaborative project with the department of infection disease we will investigate the molecular basis of the interactions between bacteria (biofilms) and human cells in (thermally-injured) human skin models co-cultured with bacteria. This will give us the opportunity to engineer an in vitro model that can be used to determine the effects of experimental medication, antibiotics and/or antimicrobial peptides.

Projects

  • Cosmetic and Pharmaceutical Industry: “Identification of biomarkers for skin aging using reconstructed human skin models”.
  • Nederlandse Brandwonden Stichting (NBS):"New strategies for the prevention and treatment of burn wound infections in skin models”. In collaboration with Dr. P.Nibbering, Infection Disease, LUMC. 
     
    HSE have been wounded with a deep wound (A) A superficial wound (B). B

a hyperprolifertaion  associated marker Keratin 17  C

Figure 3: HSE have been wounded with a deep wound (A) or superficial wound (B). A new epidermis is formed that is active in migration  and proliferation as demonstrated with a hyperprolifertaion  associated marker Keratin 17 in (C).